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PubMed1991

An investigation into the haematological toxicity of structural analogues of dapsone in-vivo and in-vitro.

With microsomes prepared from a single human liver, 4,4'-diaminodiphenyl sulphone (DDS), 4-acetyl-4-aminodiphenyl sulphone (MADDS), 4-acetyl-4-aminodiphenyl thioether (MADDT) and 4,4'-diacetyldiphenyl thioether (DADDT) caused significantly greater methaemoglobin formation compared with control. In-vitro in the rat, the pattern of toxicity was slightly different:DADDT was not haemotoxic, whilst 3,4'-diaminodiphenyl sulphone (3,4'DDS) and 3,3'-diaminodiphenyl sulphone (3,3'DDS) as well as DDS, MADDS and MADDT were significantly greater than control. 4,4' Acetyl diphenyl sulphone (DADDS), 4,4' diaminodiphenyl thioether (DDT), 4,4'-diaminodiphenyl ether (DDE) and 4,4' diaminooctofluorodiphenyl sulphone (F8DDS) did not cause significant methaemoglobinaemia in either human or rat liver microsomes. DDS, MADDS, and MADDT were not significantly different in haemotoxicity generation in-vitro in the presence of human microsomes. In the rat in-vitro, DDS, MADDS, and 3,4'DDS did not differ significantly in red cell toxicity, and were the most potent methaemoglobin formers. The 3,3'DDS and MADDT derivatives were both significantly less toxic compared with DDS. None of the compounds tested caused haemoglobin oxidation in the absence of NADPH in-vitro. In the whole rat, DDS, MADDS and MADDT caused significantly higher levels of methaemoglobin compared with control. None of the remaining compounds caused methaemoglobin formation which was significantly greater than control. DDS and MADDS were the most potent methaemoglobin formers tested, in-vivo and in-vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1982

Rapid, radiolabeled macrophage culture method for detection of dapsone-resistant Mycobacterium leprae.

Mycobacterium leprae cells extracted from the skin biopsies of 14 bacilliferous lepromatous patients were maintained in human-murine macrophage cultures for 3 weeks in the presence of [3H]thymidine and DDS (4,4'-diaminodiphenyl sulfone). All cultures except one containing freshly extracted viable bacilli showed significant incorporation of [3H]thymidine as compared to control cultures containing heat-killed bacilli of the corresponding strain. Six susceptible strains of M. leprae obtained from untreated, freshly diagnosed patients showed significant inhibition of the uptake of the radiolabel in the presence of 3 and 10 ng of DDS per ml per culture. Eight strains of M. leprae obtained from patients clinically suspected of DDS resistance were tested in a similar manner. These strains were also concurrently inoculated in the footpads of mice given orally 10(-2), 10(-3), and 10(-4) g of DDS per 100 g of body weight for 9 months. Concordant results were obtained by both methods: five strains were found to be resistant, one was susceptible, and one was partially resistant. Strain VIII did not incorporate [3H]thymidine in the macrophage cultures and proved to be resistant in the mouse footpad. The macrophage culture system provides a sensitive, rapid screening method for the early diagnosis of DDS resistance.

Adult↗